Search Results (352)

Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article

Proper subcellular localization is essential to exert the designated function of a protein, not only for endogenous proteins but also transgene-encoded proteins. Post-translational modification is a frequently used method to regulate the subcellular localization of a specific protein. While there are a number of tags that are widely used to direct the target protein to a specific location within a cell, these tags often fail to emulate the dynamics of protein trafficking, necessitating an alternative approach to the direct subcellular localization of transgene-encoded proteins. Here, we report the development of a new synthetic polypeptide protein tag comprised of ten amino acids, which promotes membrane localization of a target protein. This short synthetic peptide tag, named “Palmito-Tag”, induces ectopic palmitoylation on the cysteine residue within the tag, thereby promoting membrane localization of the target proteins without affecting their innate function. We show that the target proteins with the Palmito-Tag are incorporated into the membranous organelles within the cells, including the endosomes, as well as extracellular vesicles. Given the reversible nature of palmitoylation, the Palmito-Tag may allow us to shift the subcellular localization of the target protein in a context-dependent manner. With the advent of therapeutic applications of exosomes and other extracellular vesicles, we believe that the ability to reversibly modify a target protein and direct its deposition to the specific subcellular milieu will help us explore more effective venues to harness the potential of extracellular vesicle-based therapies. Full article

Cancer treatment has undergone a paradigm shift following the introduction of novel cancer treatment approaches that involve the host’s immune system in fighting established tumors. This new concept aids the immune system in identifying, attacking, and killing the tumor cells. However, although some encouraging results were observed clinically, this approach has its own limitations. For example, the benefits of certain anticancer drugs were only observed in some patients, off-target effects, immune evasion, and poor pharmacokinetics. Recently, several advancements have been made with the understanding and development of tumor-targeted drug delivery systems, which combine both effectiveness and patients’ safety during cancer treatment. In this review, we will focus on the latest progress in targeted drug delivery, particularly applying nanoparticles, liposomes, exosomes, and Wharton’s jelly-derived macrovesicles as immune cell enhancers, as well as overcoming therapeutic resistance. We also characterize major current problems, such as the biocompatibility and scalability of the delivered engineering systems, as well as the required regulations. Lastly, we will show some examples of effective approaches to resolve these issues for more efficient cancer therapy. The importance of this article lies in bridging two sides in a single framework perspective: the novel implementation of unique delivery systems and the latest advances in the field of cancer immunotherapy. Thus, this provides better insights for the future of cancer treatment. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, α-synuclein aggregation, and chronic neuroinflammation. Recent evidence suggests that exosomal microRNAs (miRNAs)—small, non-coding RNAs encapsulated in extracellular vesicles—are key regulators of PD pathophysiology and promising candidates for biomarker development and therapeutic intervention. Exosomes facilitate intercellular communication, cross the blood–brain barrier, and protect miRNAs from degradation, rendering them suitable for non-invasive diagnostics and targeted delivery. Specific exosomal miRNAs modulate neuroinflammatory cascades, oxidative stress, and synaptic dysfunction, and their altered expression in cerebrospinal fluid and plasma correlates with disease onset, severity, and progression. Despite their translational promise, challenges persist, including methodological variability in exosome isolation, miRNA profiling, and delivery strategies. This review integrates findings from preclinical models, patient-derived samples, and systems biology to delineate the functional impact of exosomal miRNAs in PD. We propose mechanistic hypotheses linking miRNA dysregulation to molecular pathogenesis and present an interactome model highlighting therapeutic nodes. Advancing exosomal miRNA research may transform the clinical management of PD by enabling earlier diagnosis, molecular stratification, and the development of disease-modifying therapies. Full article

This manuscript assesses the critical role of exosomal PD-L1 (ExoPD-L1) in immune suppression, tumor progression, and resistance to therapy. ExoPD-L1 has been identified as a key mediator of tumor immune evasion, contributing to systemic immunosuppression beyond the tumor microenvironment (TME) due to its capacity to travel to distant anatomical sites. In this context, the review aims to elaborate on the mechanisms by which exosomal PD-L1 interacts with T cell receptors and modulates both the tumor microenvironment and immune responses, impacting patient outcomes. We further explore emerging therapeutic strategies that target ExoPD-L1 to enhance the effectiveness of immunotherapy. Blocking ExoPD-L1 offers a novel approach to counteracting immune escape in cancer. Promising strategies include inhibiting exosome biogenesis with GW4869 or Rab inhibitors, neutralizing ExoPD-L1 with targeted antibodies, and silencing PD-L1 expression through RNA interference (RNAi) or CRISPR-based methods. While each approach presents certain limitations, their integration into combination therapies holds significant potential to improve the efficacy of immune checkpoint inhibitors. Future research should focus on optimizing these strategies for clinical application, with particular attention to improving delivery specificity and minimizing off-target effects. Full article

Exosomes are essential components produced by all cell types, originating from the endosomal pathway through the invagination of the cell membrane. Their unique physicochemical characteristics are crucial for various commercial applications. Typically, exosomes range in size from 50 to 200 nm. Exosomes derived from plant cells are larger than their animal cell counterparts and demonstrate a broader therapeutic potential. This review explores the promising research opportunities associated with plant-derived exosomes, summarizing studies on their biogenesis, characterization, isolation methods, and therapeutic applications. It also emphasizes the importance of targeted drug delivery and provides insights into engineering plant-derived exosomes with various drugs. Additionally, highlights of plant-derived exosomes as natural nano-inducers that facilitate inter-kingdom communication and cross-kingdom regulatory interactions are also elucidated herein. Henceforth, this study culminates in a multidimensional insight for innovative therapeutic strategies and biotechnological advancements in plant-derived exosome research. Full article

Circulating cell-free nucleic acids (NAs), in particular plasma-derived cell-free DNA, have evolved into promising clinical analytes for prenatal diagnostics, cancer analysis, and cancer surveillance and therapy monitoring. Nevertheless, salivary extracellular and extracellular vesicle (EV)-derived DNA and microRNA have recently gained attention as potential non-invasive biomarkers for a variety of diseases, including cancer, cardiovascular, autoimmune, and infectious diseases. Our goal in this study was therefore to evaluate and optimize commercially available approaches for cell-free nucleic acid isolation, focusing specifically on DNA and miRNA present in cell-free saliva or saliva-derived EVs. Along these lines, we investigated various commercially available kits, which enable parallel isolation of cell-free DNA and RNA in separate fractions from cell-free saliva and salivary EVs, respectively, and compared them to single analyte extraction kits. The efficiency of all tested nucleic acid extraction methods was determined by comparing DNA and RNA fluorescence spectroscopy measurements and quantitative PCR values obtained from a selection of different DNA- and microRNA targets. We found the Norgen Plasma/Serum RNA/DNA Purification Mini kit in combination with the miRCURY exosome isolation kit to work best in our hands and to provide the highest yields of EV-derived nucleic acids. Having tested and identified effective protocols for isolating salivary extracellular nucleic acids, we present with this comparison study, among others, a sound basis for future circulating small nucleic acid and epigenetic biomarker research aiming for early disease diagnosis, prognosis, and prediction from cell-free saliva, representing an easy-to-collect and readily available diagnostic fluid. Full article

Circular RNAs (circRNAs) are single-stranded noncoding RNAs with a covalently closed loop structure. They are known for their stability, abundance, and highly conserved nature. Their expression is often specific to tissues or developmental stages. They interact with microRNAs (miRNAs) and RNA-binding proteins (RBPs) and they undergo N⁶-methyladenosine (m⁶A) modifications, further affecting gene transcription and translation. Increasing evidence over the past decades has revealed that dysregulated circRNA expression is associated with various neurological disorders, particularly the glioma, one of the most malignant tumors with a poor prognosis. Due to the presence of the blood–brain barrier (BBB) and drug resistance, conventional therapeutic approaches have shown limited efficacy. Recently, increasing attention has been directed toward precisely targeted therapies, with circRNAs emerging as promising molecules for cancer treatment. Studies indicate that circRNAs play a key role in glioma proliferation and metastasis. Substantial evidence indicates that exosomes can package circRNAs and facilitate their transport across the BBB into brain tissue, highlighting the potential of circRNAs as therapeutic targets for glioma. This review summarizes circRNAs’ functional mechanisms, clinical application relevance, and current limitations. It offers future research directions in this evolving field, aiming to encourage further research on circRNAs’ therapeutic applications and contribute to the development of novel glioma-treatment strategies. Full article

Glioblastoma is a highly aggressive, infiltrative brain tumor of the central nervous system (CNS). Its extensive molecular and biochemical heterogenicity hinders the identification of reliable biomarkers and therapeutic targets, thereby making prognosis and existing therapy ineffective. In recent years, breakthroughs in the use of proteomics on a range of biological samples, such as plasma, cerebrospinal fluid (CSF), tissues, brain cells, and exosomes, represent a potential improvement to GBM investigations. Mass spectrometry-based approaches represent an important technique in the characterization of the tumoral proteome, for the identification of differentially expressed proteins, and for studying altered molecular pathways involved in tumor stages. Proteomics studies advance our knowledge about GBM pathogenesis, the discovery of reliable diagnostic and prognostic markers, and therapeutic approaches, also. In this context, for the effective application of proteomics on GBM, it is mandatory to develop a translational network by integrating hospitals, biobanks, and research institutions into a single network, to enable a collaborative approach across disciplines, thereby enabling rapid translation to clinical application of new proteomic insights. Today, high-quality biobanks play a key role in enabling collaborative, ethically compliant research, supporting the effective application of proteomics in glioblastoma studies and the translation of discoveries into clinical practice. This review explores current trends in proteomics and GBM research, highlighting how leveraging biobank infrastructure and fostering institutional cooperation can drive the development of targeted pilot projects to enhance the impact and effectiveness of glioblastoma research. Full article

The supposed meridians of traditional oriental medicine have been a cause of conflict between traditional and modern medical science. A possible resolution has been proposed: That extracellular vesicles, including exosomes, may be the transmitters of traditional therapies such as massage and acupuncture. This article develops that idea by proposing that the pathways between surface and deep structures may be laid down during the embryonic migration of cells from one region of the developing body to distant regions. This hypothesis depends on the proven targeting of vesicular communication via cell surface binding molecules and their complementary binding sites on target cells. The hypothesis is therefore experimentally testable. The article also draws attention to a strong analogy with Charles Darwin’s theory of pangenesis for particulate communication between the soma and germline. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative condition that is characterized by the accumulation of amyloid-β, the hyperphosphorylation of tau, and persistent neuroinflammation. However, these hallmarks alone do not fully capture the intricacies of AD pathology, thus necessitating the investigation of emerging mechanisms and innovative tools. Exosomes (nanoscale vesicles involved in cell communication and immune modulation) have emerged as pivotal cellular vehicles due to their dual role—both in the propagation of pathological proteins and the regulation of inflammatory responses. Furthermore, these vesicles have been demonstrated to play a crucial role in the mediation of the effects of microbiota-derived metabolites and the reflection of systemic influences such as dysbiosis, thereby establishing a link between the gut–brain axis and the progression of AD. A comprehensive narrative literature review was conducted using the following databases: ScienceDirect, Scopus, Wiley, Web of Science, Medline, and PubMed, covering studies published between 2015 and 2025. Inclusion and exclusion criteria were established to select research addressing exosomal biogenesis, their functional and diagnosis role, their therapeutic potential, and the emerging evidence on microbiota–exosome interplay in Alzheimer’s disease. Exosomes have been identified as integral mediators of intercellular communication, reflecting the molecular state of the central nervous system. These particles have been shown to promote the propagation of pathological proteins, modulate neuroinflammatory responses, and serve as non-invasive biomarkers due to their detectability in peripheral fluids. Advances in exosomal engineering and microbiome-based interventions underscore the potential for targeting systemic and CNS-specific mechanisms to develop integrative therapies for AD. Exosomes present a promising approach for the early diagnosis and personalized treatment of Alzheimer’s disease. However, methodological challenges and ongoing controversies, including those related to the influence of systemic factors such as dysbiosis, necessitate multidisciplinary research to optimize and standardize these strategies. Full article

Global growth in antimicrobial resistance (AMR) has accelerated the need for novel therapy beyond the scope of conventional antibiotics. In the last decade, polydopamine (PDA), a mussel-inspired polymer with redox capability, remarkable adhesion, and biocompatibility, has emerged as a universal antimicrobial coating with widespread uses. At the same time, extracellular vesicles (EVs) and particularly exosomes have gained prominence for their intrinsic cargo delivery and immune-modulating properties. Here, we summarize the synergistic value of PDA and exosome integration into multifunctional antimicrobial nanoplatforms. We discuss the inherent antimicrobial activity of PDA and exosomes; the advantages of PDA coating, including increased exosome stability, ROS generation, and surface functionalization; and current methodologies towards designing PDA-exosome hybrids. This review also mentions other antimicrobial polymers and nanocomposites that may be employed for exosome modification, such as quaternized chitosan, zwitterionic polymers, and polymer–metal composites. Most significant challenges, such as the maintenance of exosome integrity, coating uniformity, biocompatibility, scalability, and immunogenicity, are addressed. Finally, future research directions are highlighted, with emphasis on intelligent, stimulus-responsive coatings, AMP incorporation, and clinical translation. Collectively, this review underscores the promise of PDA-coated exosomes as potential antimicrobial therapeutics against AMR with potential applications in wound healing, implant protection, and targeted infection control. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons, leading to muscle weakness, paralysis, and ultimately respiratory failure. Despite advances in understanding its genetic basis, particularly mutations in Chromosome 9 Open Reading Frame 72 (C9orf72), superoxide dismutase 1 (SOD1), TAR DNA-binding protein (TARDBP), and Fused in Sarcoma (FUS) gene, current diagnostic methods result in delayed intervention, and available treatments offer only modest benefits. This review examines innovative approaches transforming ALS research and clinical management. We explore emerging biomarkers, including the fluid-based markers such as neurofilament light chain, exosomes, and microRNAs in biological fluids, alongside the non-fluid-based biomarkers, including neuroimaging and electrophysiological markers, for early diagnosis and patient stratification. The integration of multi-omics data reveals complex molecular mechanisms underlying ALS heterogeneity, potentially identifying novel therapeutic targets. We highlight current gene therapy strategies, including antisense oligonucleotides (ASOs), RNA interference (RNAi), and CRISPR/Cas9 gene editing systems, alongside advanced delivery methods for crossing the blood–brain barrier. By bridging molecular neuroscience with bioengineering, these technologies promise to revolutionize ALS diagnosis and treatment, advancing toward truly disease-modifying interventions for this previously intractable condition. Full article

Current therapies for Alzheimer’s disease (AD) includes acetylcholinesterase inhibitors, NMDA receptor antagonists, and amyloid beta (Aβ)/Tau-targeting drugs. While these drugs improve cognitive decline and target the pathological mechanisms, their outcomes still are still in debate. Mesenchymal stem cells (MSCs) offer a regenerative approach by modulating neuroinflammation and promoting neuroprotection. Although the paracrine of MSCs is efficient in various AD preclinical studies and the exosomes of MSCs have entered clinical trials, the key cytokines driving the efficacy remain unclear. Here, we evaluated human umbilical cord-derived MSCs (hUC-MSCs) and employed gene-silenced MSCs (siHGF-MSCs, siTNFR1-MSCs, siBDNF-MSCs) in APP/PS1 AD mice to investigate specific mechanisms. hUC-MSCs significantly reduced Aβ/Tau pathology and neuroinflammation, with cytokine-specific contributions: silencing HGF predominantly reduced Aβ/Tau clearance, although silencing TNFR1 or BDNF showed modest effects; silencing TNFR1 or BDNF more prominently weakened anti-neuroinflammation, while silencing HGF exerted a weaker influence. All three cytokines partially contributed to oxidative stress reduction and cognitive improvements. Our study highlights MSC-driven AD alleviation as a multifactorial strategy and reveals specific cytokines alleviating different aspects of AD pathology. Full article